Method for producing substituted anthranilic acid derivatives

ABSTRACT

The present invention relates to a process for preparing substituted anthranilic acid derivatives of the formula (I) 
     
       
         
         
             
             
         
       
     
     in which R 1 , R 2 , R 3  and R 4  are each as defined in the description, by conversion of compounds of the general formula (IV) in the presence of a palladium catalyst and carbon monoxide. The present invention likewise relates to compounds of the general formula (IV).

The present invention relates to a novel process for preparingsubstituted anthranilic acid derivatives of the formula (I)

in which

-   -   R¹ is optionally singly or multiply, identically or differently        fluorine- or chlorine-substituted C₁-C₆-alkyl, or C₆-C₁₀-aryl,        or is a hetaryl radical of the general formula (II)

-   -   R¹ is preferably C₁-C₃-alkyl, C₆-aryl or a hetaryl radical of        the general formula (II),    -   R¹ is more preferably C₁-C₂-alkyl or a hetaryl radical of the        general formula (II),        where    -   R⁸ is C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy,        C₁-C₄-alkylthio, C₁-C₄-alkylsulphinyl, C₁-C₄-alkylsulphonyl,        which may optionally be mono- or polysubstituted identically or        differently by fluorine or chlorine, or is fluorine, chlorine,        cyano, alkylamino, dialkylamino, cycloalkylamino or        C₃-C₆-trialkylsilyl,    -   R⁸ is preferably fluorine, chlorine or C₁-C₆-alkyl,    -   R⁸ is more preferably fluorine or chlorine,    -   Z is CH or N,    -   Z is preferably and more preferably N,        and    -   Y is hydrogen, fluorine, chlorine, optionally singly or        multiply, identically or differently fluorine- or        chlorine-substituted C₁-C₆-alkyl, C₃-C₆-cycloalkyl,        C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₁-C₄-alkylsulphinyl,        C₁-C₄-alkylsulphonyl, or is cyano, alkylamino, dialkylamino,        cycloalkylamino, C₃-C₆-trialkylsilyl or a radical of the general        formula (III)

where

-   -   R⁹ is C₁-C₅-alkyl which may optionally be mono- or        polysubstituted identically or differently by halogen,    -   R⁹ is preferably C₁-C₃ perfluoroalkyl,    -   R⁹ is more preferably CF₃ or C₂F₅,    -   R² is an OR⁵ or NR⁶R⁷ radical,    -   R² is preferably and more preferably OR⁵,    -   R² is likewise preferably and more preferably NR⁶R⁷,        where    -   R⁵, R⁶ and R⁷ are each independently hydrogen, C₁-C₆-alkyl, or        C₆-C₁₀-aryl,    -   R⁵, R⁶ and R⁷ are preferably each independently hydrogen,        C₁-C₃-alkyl or C₆-aryl,    -   R⁵, R⁶ and R⁷ are more preferably each independently hydrogen or        C₁-C₂-alkyl,    -   R³ is hydrogen, optionally singly or multiply, identically or        differently fluorine- or chlorine-substituted C₁-C₆-alkyl,        C₁-C₆-alkoxy or C₃-C₆-cycloalkyl,    -   R³ is likewise halogen,    -   R³ is preferably C₁-C₅-alkyl,    -   R³ is more preferably methyl, ethyl or tert-butyl,    -   R³ is likewise preferably and more preferably chlorine,    -   R⁴ is hydrogen, fluorine, chlorine, cyano, optionally singly or        multiply, identically or differently fluorine- or        chlorine-substituted C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio,        C₁-C₄-alkylsulphinyl, C₁-C₄-alkylsulphonyl, C₁-C₄-alkylamino,        di(C₁-C₄-alkyflamino, C₃-C₆-cycloalkylamino,        (C₁-C₄-alkoxy)imino, (C₁-C₄-alkyl)(C₁-C₄-alkoxy)imino, SF₅ or        C₃-C₆-trialkylsilyl,    -   R⁴ is preferably hydrogen, chlorine or cyano,    -   R⁴ is more preferably chlorine or cyano,        characterized in that substituted anthranilic acid derivatives        of the formula (IV)

in which the R¹, R³ and R⁴ radicals are each as defined aboveand

-   -   X is chlorine, bromine or iodine, preferably bromine or iodine,        more preferably bromine,        are reacted in the presence of a palladium catalyst and        optionally of a phosphine ligand simultaneously with carbon        monoxide and a compound of the general formula (V)

R⁵-OH   (V)

in which R⁵ is as defined aboveor a compound of the general formula (VI)

HNR⁶R⁷   (VI)

in which R⁶ and R⁷ are each as defined above.

The literature already states that it is possible to obtain substitutedanthranilic acid derivatives of the formula (I) by reaction ofanthranilic acid derivatives of the general formula (VII)

with carboxylic acids of the general formula (VIII)

R¹-COOH   (VIII)

in the presence of agents which activate the carboxyl group for thedesired reaction, for example thionyl chloride, oxalyl chloride,phosgene, methanesulphonyl chloride or toluenesulphonyl chloride (WO2003/015519; WO 2003/106427; WO 2004/067528; WO 2006/062978; WO2008/010897; WO 2008/070158; WO 2008/082502; WO 2009/006061; WO2009/061991; WO 2009/085816; WO 2009 111553; Bioorg. & Med. Chem. Lett.15 (2005) 4898-4906; Bioorg. & Med. Chem. 16 (2008) 3163-3170).

The known reactions can be illustrated by the following reactionschemes, where R¹, R³, R⁴, R⁶ and R⁷ have, for example, the definitionsgiven above:

These known methods for preparation of substituted anthranilic acidderivatives of the formula (I) require the availability of thecorresponding substituted anthranilic acid derivatives of the generalformula (VII). These substituted anthranilic acid derivatives of thegeneral formula (VII) are either known or can be prepared by knownorganic chemistry methods. Some of these substituted anthranilic acidderivatives of the general formula (VII), however, can be prepared onlyin a complex manner, in multiple stages and at high cost, which can leadto uneconomically high costs for the end products as a result ofunavoidable yield losses.

Substituted anthranilic acid derivatives of the formula (I) are of highinterest as compounds having known insecticidal efficacy (see, forexample, Bioorg. & Med. Chem. Lett. 15 (2005) 4898-4906; Biorg. & Med.Chem. 16 (2008) 3163-3170). Further, it is already known, thatsubstituted anthranilic acid derivatives of the general formula (VII)can be obtained by reacting substituted anthranilic acid derivatives ofthe general formula (IX) with carbon monoxide in the presence of apalladium catalyst, of a ligand, of a primary amine and a base (WO2012/103436). However, it is not known whether anthranilic acid amidesof the general formula (IV) can be used correspondingly.

It is therefore an object of the present invention to provide a novel,more economically viable process for preparing substituted anthranilicacid derivatives of the formula (I).

The object was achieved according to the present invention by a processfor preparing anthranilic acid derivatives of the general formula (I),characterized in that substituted anthranilic acid derivatives of thegeneral formula (IX)

in which X, R³ and R⁴ are each as defined aboveare reacted with acids of the general formula (VIII) to give thesubstituted anthranilic acid derivatives of the formula (IV)

and the latter are then reacted in the presence of a palladium catalystand optionally of a phosphine ligand simultaneously with carbon monoxideand a compound of the general formula (V)

R⁵-OH   (V)

in which R⁵ is as defined aboveor a compound of the general formula (VI)

HNR⁶R⁷   (VI)

in which R⁶ and R⁷ are each as defined aboveto give the substituted anthranilic acid derivatives of the generalformula (I).

The process according to the invention can be illustrated by thefollowing scheme:

The present invention likewise provides novel compounds of the generalformula (IV)

in which the R¹, R³, R⁴ and X radicals are each as defined above.

Preference is given to compounds of the general formula (IV) in which

-   -   R¹ is optionally singly or multiply, identically or differently        fluorine- or chlorine-substituted C₁-C₆-alkyl, or C₆-C₁₀-aryl,        or is a hetaryl radical of the general formula (II)

where

-   -   R⁸ is optionally singly or multiply, identically or differently        fluorine- or chlorine-substituted C₁-C₆-alkyl, C₃-C₆-cycloalkyl,        C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₁-C₄-alkylsulphinyl,        C₁-C₄-alkylsulphonyl, or is fluorine, chlorine, cyano,        alkylamino, dialkylamino, cycloalkylamino or        C₃-C₆-trialkylsilyl, preferably fluorine, chlorine or        C₁-C₆-alkyl, more preferably fluorine or chlorine,    -   Z is CH or N, preferably N,        and    -   Y is hydrogen, fluorine, chlorine, optionally singly or        multiply, identically or differently fluorine- or        chlorine-substituted C₁-C₆-alkyl, C₃-C₆-cycloalkyl,        C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₁-C₄-alkylsulphinyl,        C₁-C₄-alkylsulphonyl, or is cyano, alkylamino, dialkylamino,        cycloalkylamino, C₃-C₆-trialkylsilyl or a radical of the general        formula (III)

in which

-   -   R⁹ is C₁-C₅-alkyl which may be mono- or polysubstituted        identically or differently by halogen,    -   R⁹ is preferably C₁-C₃-perfluoroalkyl,    -   R⁹ is more preferably CF₃ or C₂F₅,    -   R³ is chlorine,    -   R³ is likewise methyl,    -   R⁴ is chlorine or cyano,        and    -   X is bromine or iodine.

Particular preference is given to compounds of the general formula (IV)in which

-   -   R¹ is a hetaryl radical of the general formula (II)

where

-   -   R⁸ is fluorine or chlorine,    -   Z is N,        and    -   Y is hydrogen, fluorine, chlorine or a radical of the general        formula (III)

where

-   -   R⁹ is CF₃ or C₂F₅,    -   R³ is methyl,    -   R⁴ is chlorine or cyano,        and    -   X is bromine

Examples of the particularly preferred compounds of the general formula(IV) include:

N-(2-bromo-4-cyano-6-methylphenyl)-1-(3-chloropyridin-2-yl)-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide

N-(2-bromo-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-3-{[5-(pentafluoroethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide.

General definitions: Alkyl groups substituted by one or more fluorine orchlorine atoms (=fluoro- or chloroalkyl groups) are selected, forexample, from trifluoromethyl (CF₃), difluoromethyl (CHF₂), CCl₃, CFCl₂,CF₃CH₂, ClCH₂, CF₃CCl₂.

Alkyl groups in the context of the present invention, unless defineddifferently, are linear or branched hydrocarbyl groups.

The definition alkyl and C₁-C₁₂-alkyl encompasses, for example, themeanings of methyl, ethyl, n-, isopropyl, n, iso-, sec- and t-butyl,n-pentyl, n-hexyl, 1,3-dimethylbutyl, 3,3-dimethylbutyl, n-heptyl,n-nonyl, n-decyl, n-undecyl, n-dodecyl.

Cycloalkyl groups in the context of the present invention, unlessdefined differently, are cyclic saturated hydrocarbyl groups.

Aryl radicals in the context of the present invention, unless defineddifferently, are aromatic hydrocarbyl radicals which may have one, twoor more heteroatoms selected from O, N, P and S and may optionally besubstituted by further groups.

Arylalkyl groups and arylalkoxy groups in the context of the presentinvention, unless defined differently, are, respectively, alkyl andalkoxy groups which are substituted by aryl groups and may have analkylene chain. Specifically, the definition arylalkyl encompasses, forexample, the meanings of benzyl and phenylethyl, and the definitionarylalkoxy, for example, the meaning of benzyloxy.

Alkylaryl groups (alkaryl groups) and alkylaryloxy groups in the contextof the present invention, unless defined differently, are, respectively,aryl groups and aryloxy groups which are substituted by alkyl groups,may have a C₁₋₈-alkylene chain and may have, in the aryl skeleton oraryloxy skeleton, one or more heteroatoms selected from O, N, P and S.

Step 1

Anthranilic acid derivatives of the formula (IV) can be prepared asfollows:

The reaction is performed in the presence of a condensing agent.Suitable agents for this purpose are all agents customary for suchcoupling reactions. Examples include acid halide formers such asphosgene, phosphorus tribromide, phosphorus trichloride, phosphoruspentachloride, phosphorus oxychloride, oxalyl chloride or thionylchloride; anhydride formers such as ethyl chloroformate, methylchloroformate, isopropyl chloroformate, isobutyl chloroformate ormethanesulphonyl chloride; carbodiimides such asN,N′-dicyclohexylcarbodiimide (DCC) or other customary condensing agentssuch as phosphorus pentoxide, polyphosphoric acid,1,1′-carbonyldiimidazole, 2-ethoxy-N-ethoxycarbonyl-1,2-dihydroquinoline(EEDQ), triphenylphosphine/carbon tetrachloride,bromotripyrrolidinophosphonium hexafluorophosphate,bis(2-oxo-3-oxazolidinyl)phosphine chloride orbenzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate.It is likewise possible to use polymer-supported reagents, for examplepolymer-bound cyclohexylcarbodiimide

Preference is given to phosgene, mesyl chloride and thionyl chloride.

Process step 1 can optionally be performed in the presence of an inertorganic diluent customary for such reactions. These preferably includealiphatic, alicyclic or aromatic hydrocarbons, for example petroleumether, hexane, heptane, cyclohexane, methylcyclohexane, benzene,toluene, xylene or decalin; halogenated hydrocarbons, for examplechlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbontetrachloride, dichloroethane or trichloroethane; ethers such as diethylether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amylether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethaneor anisole; ketones such as acetone, butanone, methyl isobutyl ketone orcyclohexanone; nitriles such as acetonitrile, propionitrile, n- orisobutyronitrile or benzonitrile; amides such as N,N-dimethylformamide,N,N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone orhexamethylphosphoramide, or mixtures thereof.

Process step 1 is generally performed in the presence of a base.

Suitable bases are alkali metal hydroxides, for example lithiumhydroxide, sodium hydroxide or potassium hydroxide, alkali metalcarbonates, for example Na₂CO₃, K₂CO₃, and acetates, for example NaOAc,KOAc, LiOAc, and also alkoxides, for example NaOMe, NaOEt, NaOt-Bu,KOt-Bu. Likewise suitable bases are organic bases such astrialkylamines, alkylpyridines, phosphazenes and1,8-diazabicyclo[5.4.0]undecene (DBU). Preference is given to organicbases such as pyridines, alkylpyridines, for example2,6-dimethylpyridine, 2-methyl-5-ethylpyridine or 2,3-dimethylpyridine.

Process step 1 of the invention is performed preferably within atemperature range from 20° C. to +100° C., more preferably attemperatures of 30° C. to +80 ° C., more preferably at 30-60° C.

Process step 1 of the invention is generally performed under standardpressure. Alternatively, however, it is also possible to work undervacuum or under elevated pressure in an autoclave.

The reaction time may, according to the batch size and the temperature,be selected within a range between 1 hour and several hours.

Process step 1 can optionally be performed in the presence of acatalyst. Examples include 4-dimethylaminopyridine or1-hydroxybenzotriazole.

Step 2

Substituted anthranilic acid derivatives of the general formula (1) canbe prepared in accordance with process step 2 as follows:

The reaction is performed in the presence of a palladium catalyst. Thepalladium catalysts used in the process according to the invention arepalladium(II) salts, for instance palladium chloride, bromide, iodide,acetate or acetylacetonate, which may optionally be stabilized byfurther ligands, for example alkyl nitriles, or Pd(O) species, forexample palladium on activated carbon, Pd(PPh₃)₄,bis(dibenzylideneacetone)palladium ortris(dibenzylideneacetone)dipalladium. Preference is given tobis(dibenzylideneacetone)palladium,tris(dibenzylideneacetone)dipalladium, palladium chloride, palladiumbromide and palladium acetate; particular preference is given tobis(dibenzylideneacetone)palladium, palladium chloride and palladiumacetate.

The amount of palladium catalyst used in the process according to theinvention is 0.001 to 20 mole percent, based on substituted anthranilicacid derivative of the general formula (IV) used. Preferably 0.005 to 10mole percent is used, more preferably 0.01 to 5 mole percent.

The phosphine ligands used in the process according to the invention areligands of the general formula (X)

PR¹⁰R¹¹R¹²   (X)

where the R¹⁰, R¹¹ and R¹² radicals are each independently hydrogen,linear or branched C₁-C₈-alkyl, vinyl, aryl or heteroaryl from the groupof pyridine, pyrimidine, pyrrole, thiophene and furan, which may in turnbe substituted by further substituents from the group of linear orbranched C₁-C₈-alkyl or C₆-C₁₀-aryl, linear or branched C₁-C₈-alkyloxyor C₁-C₁₀-aryloxy, halogenated linear or branched C₁-C₈-alkyl orhalogenated C₆-C₁₀-aryl, C₆-C₁₀ -aryloxycarbonyl, linear or branchedC₁-C₈-alkylamino, linear or branched C₁-C₈-dialkylamino,C₁-C₈-arylamino, C₁-C₈-diarylamino, hydroxyl, carboxyl, cyano andhalogen such as fluorine or chlorine.

Further useful phosphine ligands include chelating bisphosphines.Examples of these include 1,2-bis(diphenylphosphino)ethane,1,2-bis(diphenylphosphino)propane, 1,2-bis(diphenylphosphino)butane,2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 1,1′-bis(diphenylphosphino)ferrocene.

Preferred phosphine ligands are trialkylphosphines such astri-tert-butylphosphine and triadamantylphosphine, and alsotriarylphosphines such as triphenylphosphine, tri(ortho-tolyl)phosphineor tri(para-methoxyphenyl)phosphine. Particular preference is given totriphenylphosphine.

As an alternative to this, it is also possible to use defined palladiumcomplexes which have been obtained from the abovementioned ligands inone or more process steps.

In the process according to the invention, 1-20 molar equivalents ofphosphine are used, based on the amount of palladium used. Preferably2-15 molar equivalents are used.

Process step 2 of the process according to the invention is performed inthe presence of carbon monoxide (CO). The carbon monoxide is typicallyintroduced in gaseous form, and so the reaction is usually performed inan autoclave. It is customary to work at CO pressure 0.1 to 50 bar,preferably at 1 to 25 bar.

It is alternatively also possible in principle to introduce the carbonmonoxide in the form of suitable metal carbonyl complexes, for exampledicobalt octacarbonyl or molybdenum hexacarbonyl. Preference is given toworking with gaseous carbon monoxide.

Process step 2 is generally performed in the presence of a base.Suitable bases are organic bases such as trialkylamines, alkylpyridines,phosphazenes and 1,8-diazabicyclo[5.4.0]undecene (DBU). Preference isgiven to organic bases such as triethylamine, tripropylamine,tributylamine, diisopropylethylamine, pyridine, alkylpyridines, forexample 2,6-dimethylpyridine, 2-methyl-5-ethylpyridine or2,3-dimethylpyridine.

The compounds of the general formula (V) or (VI) required forpreparation of the substituted anthranilic acid derivatives of thegeneral formula (I) are typically used in an excess, based on thesubstituted anthranilic acid derivative of the general formula (IV). Itis also possible to use the compounds of the general formula (V) or (VI)in such an amount that they simultaneously serve as solvents.

PREPARATION EXAMPLES

The Preparation Examples which follow illustrate the invention withoutlimiting it.

Example 1 2-Acetamido-5-cyano-3-methylbenzoic Acid

In a 30 ml autoclave, under nitrogen as protective gas, 2.54 g [10 mmol]of N-(2-bromo-4-cyan-6-methylphenyl)acetamide, 3.89 g [21 mmol] oftri-n-butylamine, 0.131 g [0.5 mmol] of triphenylphosphine, 0.035 g[0.05 mmol] of bis(triphenylphosphine)palladium(II) chloride and 2 g ofwater are combined. After closure, the autoclave is purged with carbonmonoxide and heated to 110° C., and a carbon monoxide pressure of 10 baris maintained After 18 hours, the mixture is allowed to cool to roomtemperature, the autoclave is depressurized, the reaction mixture isstirred with methylene chloride and filtered through kieselguhr, and thefiltrate is washed, first with dilute hydrochloric acid and then withwater, dried over sodium sulphate and concentrated under reducedpressure. This gives 1.14 g of the title compound.

LC/MS: m/e=219 (MH⁺).

GC/MS(sil.): m/e=362 (M⁺, 2×sil., 10%), 347 (M⁺−15, 2×sil., 45%).

Example 2N-(2-Bromo-4-cyano-6-methylphenyl)-1-(3-chloropyridin-2-yl)-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide

To a solution of 3.74 g of1-(3-chloropyridin-2-yl)-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxylicacid in 20 ml of acetonitrile are added 1.86 g of 3-methylpyridine. Then1.37 g of methanesulphonyl chloride are added dropwise at 0° C. After 30minutes at 0° C., the red solution thus obtained is slowly addeddropwise to a solution of 2.11 g of 4-amino-3-bromo-5-methylbenzonitrileand 1.12 g of 3-methylpyridine in 20 ml of acetonitrile. The reactionmixture is stirred at room temperature for one hour and at 40° C. for 1hour and cooled to room temperature, water and methylene chloride areadded thereto, and the organic phase is removed, washed with dilutehydrochloric acid, dried and concentrated. The crude product thusobtained is purified by chromatography on silica gel (cyclohexane/ethylacetate). This gives 1.30 g of the title compound as a pale beige solid.

LC/MS: m/e=566 (MH⁺ with ⁷⁹Br and ³⁵Cl).

Example 3 Methyl2-({[1-chloropyridin-2-yl)-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazol-5-yl]carbonyl}amino)-5-cyano-3-methylbenzoate

In a 30 ml autoclave, under nitrogen as protective gas, 0.567 g ofN-(2-bromo-4-cyano-6-methylphenyl)-1-(3-chloropyridin-2-yl)-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide, 0.463 g of tri-n-butylamine, 0.066 gof triphenylphosphine, 0.035 g of bis(triphenylphosphine)palladium(II)chloride and 10 ml of methanol are combined. After closure, theautoclave is purged with carbon monoxide and heated to 110° C., and acarbon monoxide pressure of 10 bar is maintained. After 18 hours, themixture is allowed to cool to room temperature, the autoclave isdepressurized, the reaction mixture is stirred with methylene chlorideand filtered through kieselguhr, and the filtrate is washed, first withdilute hydrochloric acid and then with water, dried over sodium sulphateand concentrated under reduced pressure. This gives 0.49 g of the titlecompound.

LC/MS: m/e=546 (MH⁺ with ³⁵Cl).

Example 41-(3-Chloropyridin-2-yl)-N-[4-cyano-2-(dimethylcarbamoyl)-6-methylphenyl]-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide

In a 30 ml autoclave, under nitrogen as protective gas, 0.567 g ofN-(2-bromo-4-cyano-6-methylphenyl)-1-(3-chloropyridin-2-yl)-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide,0.463 g of tri-n-butylamine, 0.066 g of triphenylphosphine, 0.035 g ofbis(triphenylphosphine)palladium(II) chloride and 2 ml of dimethylamineare combined. After closure, the autoclave is purged with carbonmonoxide and heated to 110° C., and a carbon monoxide pressure of 10 baris maintained. After 18 hours, the mixture is allowed to cool to roomtemperature, the autoclave is depressurized, the reaction mixture isstirred with methylene chloride and filtered through kieselguhr, and thefiltrate is washed, first with dilute hydrochloric acid and then withwater, dried over sodium sulphate and concentrated under reducedpressure. This gives 0.475 g of the title compound.

LC/MS: m/e=559 (MH⁺ with ³⁵Cl).

1. Process for preparing a compound of formula (I)

in which R¹ is optionally singly or multiply, identically or differentlyfluorine- or chlorine-substituted C₁-C₆-alkyl, or C₆-C₁₀-aryl, or is ahetaryl radical of formula (II)

where R⁸ is C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy,C₁-C₄-alkylthio, C₁-C₄-alkylsulphinyl, C₁-C₄-alkylsulphonyl, which mayoptionally be mono- or polysubstituted, identically or differently byfluorine or chlorine, or is fluorine, chlorine, cyano, alkylamino,dialkylamino, cycloalkylamino or C₃-C₆-trialkylsilyl, Z is CH or N, andY is hydrogen, fluorine, chlorine, optionally singly or multiply,identically or differently fluorine- or chlorine-substitutedC₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio,C₁-C₄-alkylsulphinyl, C₁-C₄-alkylsulphonyl, or is cyano, alkylamino,dialkylamino, cycloalkylamino, C₃-C₆-trialkylsilyl or a radical offormula (III)

where R⁹ is C₁-C₅-alkyl which may optionally be mono- or polysubstitutedidentically or differently by halogen, R² is an OR⁵ or NR⁶R⁷ radical,where R⁵, R⁶ and R⁷ are each independently hydrogen, C₁-C₆-alkyl, orC₆-C₁₀-aryl, R³ is hydrogen, optionally singly or multiply, identicallyor differently fluorine- or chlorine-substituted C₁-C₆-alkyl,C₁-C₆-alkoxy or C₃-C₆-cycloalkyl, R⁴ is hydrogen, fluorine, chlorine,cyano, optionally singly or multiply, identically or differentlyfluorine- or chlorine-substituted C₁-C₄-alkyl, C₁-C₄-alkoxy,C₁-C₄-alkylthio, C₁-C₄-alkylsulphinyl, C₁-C₄-alkylsulphonyl,C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino, C₃-C₆-cycloalkylamino,(C₁-C₄-alkoxy)imino, (C₁-C₄-alkyl)(C₁-C₄-alkoxy)imino, SF₅ orC₃-C₆-trialkylsilyl, comprising reacting a substituted anthranilamidederivative of the formula (IV)

in which the R¹, R³ and R⁴ radicals are each as defined above and X ischlorine, bromine or iodine, in the presence of a palladium catalyst andoptionally of a phosphine ligand simultaneously with carbon monoxide anda compound of formula (V)R⁵—OH   (V) in which R⁵ is as defined above or a compound of formula(VI)HNR⁶R⁷   (VI) in which R⁶ and R⁷ are each as defined above.
 2. Processaccording to claim 1, wherein the compound of formula (IV) is preparedby reacting a Compound of formula (IX)

in which X, R³ and R⁴ are each as defined above with acids of formula(VIII)R¹COOH   (VIII) in which R¹ is as defined above.
 3. Process according toclaim 2, wherein the compound of formula (IV) is prepared in thepresence of a condensing agent and of a base.
 4. Process according toclaim 1, wherein the palladium catalyst used is a palladium (II) saltand/or Pd(O) species.
 5. Process according to claim 4, wherein thepalladium catalyst used is bis(dibenzylideneacetone)palladium,tris(dibenzylideneacetone)dipalladium, palladium chloride, palladiumbromide and/or palladium acetate.
 6. Process according to claim 1,wherein the phosphine ligand used is a compound of formula (X)PR¹⁰R¹¹R¹²   (X) where the R¹⁰, R¹¹ and R¹² radicals are eachindependently hydrogen, linear or branched C₁-C₈-alkyl, vinyl, aryl orheteroaryl selected from pyridine, pyrimidine, pyrrole, thiophene andfuran, which may in turn be substituted by further substituents from thegroup of linear or branched C₁-C₈-alkyl or C₆-C₁₀-aryl, linear orbranched C₁-C₈-alkyloxy or C₁-C₁₀-aryloxy, halogenated linear orbranched C₁-C₈-alkyl or halogenated C₆-C₁₀-aryl, C₆-C₁₀-aryloxycarbonyl,linear or branched C₁-C₈-alkylamino, linear or branchedC₁-C₈-dialkylamino, C₁-C₈-arylamino, C₁-C₈-diarylamino, hydroxyl,carboxyl, cyano and halogen, or a chelating biphosphine.
 7. Processaccording to claim 6, wherein the chelating biphosphine is one or moreselected from 1,2-bis(diphenylphosphino)ethane,1,2-bis(diphenylphosphino)propane, 1,2-bis(diphenylphosphino)butane,2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and1,1′-bis(diphenylphosphino)ferrocene.
 8. Process according to claim 6,wherein the phosphine ligand used is triphenylphosphine.
 9. Processaccording to claim 6, wherein 1-20 molar equivalents of phosphine areused, based on the amount of palladium catalyst used.
 10. Compound offormula (IV)

Where R¹ is optionally singly or multiply, identically or differentlyfluorine- or chlorine-substituted C₁-C₆-alkyl, or C₆-C₁₀-aryl, or is ahetaryl radical of formula (II)

where R⁸ is C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy,C₁-C₄-alkylthio, C₁-C₄-alkylsulphinyl, C₁-C₄-alkylsulphonyl, which mayoptionally be mono- or polysubstituted, identically or differently byfluorine or chlorine, or is fluorine, chlorine, cyano, alkylamino,dialkylamino, cycloalkylamino or C₃-C₆-trialkylsilyl, Z is CH or N, andY is hydrogen, fluorine, chlorine, optionally singly or multiply,identically or differently fluorine- or chlorine-substitutedC₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio,C₁-C₄-alkylsulphinyl, C₁-C₄-alkylsulphonyl, or is cyano, alkylamino,dialkylamino, cycloalkylamino, C₃-C₆-trialkylsilyl or a radical offormula (III)

where R⁹ is C₁-C₅-alkyl which may optionally be mono- or polysubstitutedidentically or differently by halogen, R² is an OR⁵ or NR⁶R⁷ radical,where R⁵, R⁶ and R⁷ are each independently hydrogen, C₁-C₆-alkyl, orC₆-C₁₀-aryl, R³ is hydrogen, optionally singly or multiply, identicallyor differently fluorine- or chlorine-substituted C₁-C₆-alkyl,C₁-C₆-alkoxy or C₃-C₆-cycloalkyl, R⁴ is hydrogen, fluorine, chlorine,cyano, optionally singly or multiply, identically or differentlyfluorine- or chlorine-substituted C₁-C₄-alkyl, C₁-C₄-alkoxy,C₁-C₄-alkylthio, C₁-C₄-alkylsulphinyl, C₁-C₄-alkylsulphonyl,C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino, C₃-C₆-cycloalkylamino,(C₁-C₄-alkoxy)imino, (C₁-C₄-alkyl)(C₁-C₄-alkoxy)imino, SF₅ orC₃-C₆-trialkylsilyl.
 11. Compound of formula (IV) according to claim 10,where R¹ is optionally singly or multiply, identically or differentlyfluorine- or chlorine-substituted C₁-C₆-alkyl, or C₆-C₁₀-aryl, or is ahetaryl radical of the general formula (II)

where R⁸ is optionally singly or multiply, identically or differentlyfluorine- or chlorine-substituted C₁-C₆-alkyl, C₃-C₆-cycloalkyl,C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₁-C₄-alkylsulphinyl,C₁-C₄-alkylsulphonyl, or is fluorine, chlorine, cyano, alkylamino,dialkylamino, cycloalkylamino or C₃-C₆-trialkylsilyl, Z is CH or N, andY is hydrogen, fluorine, chlorine, C₁-C₆-alkyl, C₃-C₆-cycloalkyl,C₁-C₆-fluoro- or -chloroalkyl, C₁-C₆-fluoro- or -chlorocycloalkyl,C₁-C₄-alkoxy, C₁-C₄-fluoro- or -chloroalkoxy, C₁-C₄-alkylthio,C₁-C₄-alkylsulphinyl, C₁-C₄-alkylsulphonyl, C₁-C₄-fluoro- or-chloroalkylthio, C₁-C₄-fluoro- or -chloroalkylsulphinyl, C₁-C₄-fluoro-or -chloroalkylsulphonyl, cyano, alkylamino, dialkylamino,cycloalkylamino, C₃-C₆-trialkylsilyl or a radical of the general formula(III)

in which R⁹ is C₁-C₅-alkyl which may be mono- or polysubstitutedidentically or differently by halogen, R³ is methyl, R³ is likewisechlorine, R⁴ is chlorine or cyano, and X is bromine or iodine. 12.Compound of formula (IV) according to claim 10, where R¹ is a hetarylradical of the general formula (II)

where R⁸ is fluorine or chlorine, Z is N, and Y is hydrogen, fluorine,chlorine or a radical of the general formula (III)

where R⁹ is CF₃ or C₂F₅, R³ is methyl, R⁴ is chlorine or cyano, and X isbromine.